LINE‐1 Retroelement Activation and Neuroinflammation in Persons With Fanconi Anemia

We describe the first immunohistochemical analysis performed on brain lesion biopsies from two young individuals with Fanconi anemia neuroinflammatory syndrome (FANS). We identified aberrant activation of the LINE-1 retrotransposon as a novel mechanism of neuroinflammation in individuals with hematological disorders. LINE-1 ORF-1 protein is upregulated in biopsies of inflammatory lesions compared to brain tissue from persons with FA without FANS, and shows activation of an innate immune response with increased STING and IFI6 expression. Awareness among hematologists is vital, as this condition can mimic an aggressive brain tumor both clinically and radiographically, and the proposed mechanism has meaningful therapeutic implications.